Ataxia and cerebellar anomalies - narrow panel

Gene: WSB2

I don't know

Comment on list classification: There are only two unrelated patients reported with cerebellar hypoplasia. There is also functional evidence available from mouse model, which does not provide any details on cerebellar abnormalities. Hence, this gene should be rated amber with current evidence. The 'watchlist' tag is added.

Created: 2 Jan 2026, 2:42 p.m. | Last Modified: 2 Jan 2026, 2:42 p.m.

Panel Version: 8.43

PMID:40374945 reported five patients from four unrelated families with developmental delays, brain anomalies, and dysmorphic features with or without intrauterine growth restriction (IUGR) and hypotonia. They were all identified with homozygous predicted loss-of-function (pLoF) or missense variants in WSB2 gene (c.128G>A/ p.Trp43Ter, p.Gln134ArgfsTer14, c.1121G>A/ p.Arg374Gln & c.1187_1188delAA/ p.Lys396ArgfsTer19) inherited from asymptomatic consanguineous parents.

Although brain abnormalities were reported in four of five patients, cerebellar hypoplasia and/ or atrophy was only reported in two patients.

There is also functional evidence available from Wsb2-mutant mice, which exhibited several neurological findings that included hyperactivity, altered exploration, and hyper alertness. They also weighed less, had a lower heart rate, and presented an abnormal retinal blood vessel morphology and vasculature pattern along with decreased total thickness of the retina.

This gene has not been associated with relevant phenotypes either in OMIM, Gene2Phenotype or ClinGen.
Sources: Literature

Created: 2 Jan 2026, 2:35 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 40374945